Nephrolithiasis

Nephrolithiasis (kidney stones) results from supersaturation of urine with lithogenic solutes that exceeds the capacity of urinary inhibitors to prevent crystallization. Stone formation follows a sequence: nucleation (initial crystal formation when solute concentration exceeds the metastable supersaturation threshold), crystal growth (accretion of additional solute onto the crystal lattice), aggregation (crystals clump together), and retention (crystals anchor to the urothelium, particularly at Randall plaques — subepithelial hydroxyapatite deposits on renal papillae that serve as nidi for calcium oxalate stone formation). Calcium oxalate stones (70-80% of all stones) form when urinary calcium and oxalate concentrations exceed saturation, promoted by hypercalciuria (absorptive, resorptive from hyperparathyroidism, or renal leak), hyperoxaluria (dietary or enteric from fat malabsorption binding calcium in the gut, freeing oxalate for absorption), hypocitraturia (citrate is the primary endogenous inhibitor, chelating urinary calcium and inhibiting crystal growth), and low urine volume. Calcium phosphate stones (brushite, hydroxyapatite) form in alkaline urine (pH greater than 6.5), often associated with distal renal tubular acidosis or primary hyperparathyroidism. Uric acid stones (5-10%) form in persistently acidic urine (pH less than 5.5) because uric acid has a pKa of 5.35 — below this pH, uric acid is in its insoluble protonated form. Struvite stones (magnesium ammonium phosphate) form exclusively in the setting of urease-producing bacterial infections (Proteus mirabilis, Klebsiella, Pseudomonas): bacterial urease hydrolyzes urea to ammonia, alkalinizing urine to pH greater than 7.2 and creating supersaturation with struvite; these stones can grow rapidly into staghorn calculi filling the renal pelvis and calyces. Cystine stones (1-2%) result from autosomal recessive cystinuria, causing defective proximal tubular reabsorption of cystine and other dibasic amino acids. Acute renal colic occurs when a stone obstructs the ureter, causing ureteral spasm and distension with sudden-onset severe flank pain radiating to the groin, accompanied by hematuria. Common sites of ureteral obstruction correspond to anatomical narrowing: the ureteropelvic junction, the pelvic brim where the ureter crosses the iliac vessels, and the ureterovesical junction.